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Updated: May 14, 2026
09:29
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
ERα-Independent Activity of Tamoxifen-Based Transition Metal Hybrids in Triple-Negative Breast Cancer Models In Vitro
Blagoje Murganić1, Tamara Krajnović2, Duško Dunđerović3
1Department of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences "Vinča", National Institute of Republic of Serbia, University of Belgrade, 11351 Belgrade, Serbia.
Molecules (Basel, Switzerland)
|May 13, 2026
Summary
Metal-tamoxifen hybrids show enhanced antitumor activity in triple-negative breast cancer (TNBC) models. Copper-tamoxifen demonstrated superior tumor reduction in vivo, while tamoxifen alone revealed significant immune cell infiltration, suggesting alternative therapeutic mechanisms.
Area of Science:
- Oncology
- Materials Science
- Pharmacology
Background:
- Triple-negative breast cancer (TNBC) is notoriously difficult to treat with endocrine therapy.
- Metal-tamoxifen conjugates have shown promise in amplifying antitumor activity.
- Understanding the mechanisms of these conjugates is crucial for TNBC treatment.
Purpose of the Study:
- To evaluate the efficacy of metal-tamoxifen hybrids against TNBC.
- To compare the cytotoxic profiles and in vivo antitumor potential of palladium (Pd), copper (Cu), and platinum (Pt)-based tamoxifen conjugates.
- To investigate the underlying mechanisms, including oxidative burst and immune response.
Main Methods:
- In vitro cytotoxicity assays using TNBC cell lines.
- Measurement of oxidative burst using fluorescent probes (DAF-FM, DHE, DHR-123).
- In vivo studies using orthotopic syngeneic mouse models to assess tumor reduction and immune cell infiltration.
Main Results:
- Pd- and Cu-tamoxifen hybrids exhibited superior sustained cytotoxicity and induced a significant oxidative burst compared to Pt-based counterparts in vitro.
- In vivo, Cu-tamoxifen showed potent tumor reduction, though limited by toxicity.
- Surprisingly, tamoxifen alone demonstrated remarkable in vivo tumor reduction, associated with significant lymphocyte infiltration, suggesting immune-mediated effects.
Conclusions:
- Metal-tamoxifen conjugates, particularly Cu- and Pd-based, offer enhanced efficacy against TNBC.
- Tamoxifen's inherent immune-modulating properties may contribute significantly to its in vivo antitumor effects, independent of direct cytotoxicity.
- Further research into tamoxifen's immunotherapeutic potential is warranted for TNBC treatment strategies.
